This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Plasmodium vivax is the most prevalent human malarial parasite in several areas of Asia and South-Central America. Phylogenetic studies have shown that P. vivax and other Plasmodium spp. currently found in Southeast Asian macaques are part of a monophyletic group from which P. vivax originated as a human parasite as a result of a host switch. The proposed investigation seeks to understand the evolutionary history of P. vivax together with its known sister taxa in Southeast Asian macaques. Understanding the evolutionary history of macaque malarias is important because some of these parasites can infect humans. Overall, the proposed investigation aims to understand the role of positive selection in the evolution of proteins expressed during erythrocyte invasion in P. vivax and related species. This is a critical step in the parasite life cycle. Several of these proteins are considered targets for malaria vaccines. Spurious evidence of positive selection, however, could result from demographic processes (such as population growth and population structure). Thus we propose to assess the demographic histories of P. vivax and macaque Plasmodium spp., using extensive geographic sampling to understand the evolution of putative adaptive variation. We are just beginning the 2nd year of this 4 year project and have sampled macaques extensively in Lombok and Singapore. Plans are underway to expand the research into Cambodia where the malaria ecology of the primates and humans is poorly characterized.